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Biomedical subjects

G W James

Publications and source records attributed to G W James.

At least 37 records · Page 2Linked to original sources
PubMed1976

Translation of human globin mRNA: globin synthesis in cells containing Hb Leiden.

Most structurally abnormal hemoglobins are present in smaller amounts than HbA in the erythrocytes of heterozygous subjects. In the presence of a hemoglobinopathy, alpha and beta globin synthesis remains balanced with equal production of the two types of chains. In reticulocytes of subjects with Hb Leiden (beta 6 or 7 glu leads to 0) there is greater production of alpha than beta globin in vitro (beta/alpha = 0.67), and slightly more beta A is synthesized than beta Leiden (beta A/beta Leiden = 1.28). Differences in specific mRNA content, rates of initiation of chain synthesis, or rates of chain elongation could be responsible for such differential polypeptide synthesis. In the present study, the ribosomal assembly of beta A, beta Leiden, and alpha globin chains was examined in peripheral blood. The translation times of the three chains did not differ significantly (average times: beta A = 65.4 sec, beta Leiden = 70.8 sec, alpha = 53.5 sec). These results indicated that an altered rate of translation was not the source of the anomalous globin synthesis observed in vitro in cells containing Hb Leiden. The experiments suggested that the observed imbalance in alpha/beta production was due to either differential rates of initiation of globin chain synthesis or quantitative differences in the amounts of the specific mRNAs present in the cells.

Cell-Free System↗
PubMed1975

An investigation and some parameters that affect the galactosamine model of hepatitis in the rat.

1. The effect of d-galactosamine hydrochloride on the livers of rats was observed by measuring serum transaminase levels and histological examination. 2. Galactosamine caused dose related liver cell damage when given i.p. and s.c. but was ineffective when given orally. 3. The time of maximum effect was 24--48 h after administration. 4. The liver cell damage was modified by the oestrus cycle in female rats. 5. Galactosamine when given in proportion to body weight tended to be less effective as body weight increased.

Administration, Oral↗
PubMed1974

Imbalance in alpha and beta globin synthesis associated with a hemoglobinopathy.

In contrast to findings in the thalasemia syndromes, studies of globin synthesis in subjects with structurally abnormal hemoglobins have generally revealed equal production of alpha and beta polypeptide chains. However, in the present investigation of globin biosynthesis in vitro in blood and marrow from two subjects heterozygous for unstable hemoglobin Leiden, beta6 or 7 Glu --> O, a significant excess of alpha-chain production was revealed. A mother and daughter of northern European ancestry with mild compensated hemolytic anemia were found to have 25% hemoglobin Leiden. Increased hemolysis occurred after the ingestion of a sulfonamide and during infections. Normal levels of hemoglobin A2, 3.0 and 2.7%, and hemoglobin F, 0.8 and 0.6%, were found in the two subjects. Similar percentages of the minor hemoglobins were demonstrated in other family members without hemoglobin Leiden. After incubation of peripheral blood with [(3)H]-leucine, the beta(A)/beta(Leiden) synthesis ratio was 1.3, and the specific activity of beta(Leiden) was 1.3-2 times beta(A). These results indicate preferential destruction of the unstable hemoglobin Leiden. However, in contrast to previous studies of other unstable hemoglobins, there was excess synthesis of alpha-chains. The total beta/alpha synthesis ratio was 0.47-0.63 in peripheral blood and 0.82 in marrow. A pool of free alpha-chains was demonstrated by starch gel electrophoresis and DEAE column chromatography. The synthesis of globin chains was balanced in family members without hemoglobin Leiden. This degree of predominance of alpha-chain synthesis in subjects with hemoglobin Leiden resembles the findings in heterozygous beta-thalassemia. However, the relatively normal hemoglobin content of the cells with this abnormal hemoglobin suggests the possibility of an absolute excess alpha-chain production in the hemoglobin Leiden syndrome.

Adult↗
PubMed1972

The inhibition by dexamethasone and disodium cromoglycate of anaphylactic bronchoconstriction in the rat.

1. A method for the measurement of anaphylactic bronchoconstriction in the rat is described.2. Dexamethasone inhibited this response in a dose-related manner.3. Disodium cromoglycate antagonized the response. A bell-shaped dose-response curve was obtained with peak activity at 1 mg/kg i.v.4. Meclofenamate was not active when given alone or in combination with dexamethasone.5. Methysergide significantly inhibited the response. Mepyramine, atropine, propranolol and adrenalectomy did not significantly modify the response.6. The relationships of anaphylactic bronchoconstriction in the rat to anaphylactic bronchoconstriction in the guinea-pig and to human asthma are discussed.

Adrenalectomy↗
PubMed1968

Antagonism by fenamates and like-acting drugs of bronchoconstriction induced by bradykinin or antigen in the guinea-pig.

1. Nine non-steroidal anti-inflammatory drugs were tested for antagonism of bradykinin-induced bronchoconstriction in guinea-pig lungs in vivo. Only one, benzydamine, was inactive.2. The descending order of potency of the active anti-inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>glafenine>ibufenac.3. Of eight other drugs tested, chlorpromazine, phenoxybenzamine and four others were inactive, whereas phenelzine and mebanazine possessed activity.4. In tests at two dose-levels of meclofenamate, the dose-ratio of bradykinin increased proportionately with the dose of meclofenamate.5. The anti-bradykinin effect of meclofenamate was still observed after destruction of the brain and spinal cord, after bilateral adrenalectomy or after blockade of beta-receptors for adrenaline.6. Meclofenamate did not release catecholamines from the adrenal medulla or prevent such a release by bradykinin given intra-arterially.7. The fenamates and like-acting drugs reduced the intensity of anaphylactic bronchoconstriction in guinea-pigs treated with mepyramine or propranolol. The descending order of potency was meclofenamate>flufenamate>mefenamate.8. Dose / response curves for the antagonism of anaphylactic bronchoconstriction by the fenamates, in the presence of propranolol, turned downwards at high doses.9. These findings suggest that the fenamates may find a useful place in the treatment of bronchial asthma or other conditions involving allergic ventilatory impairment.

Adrenal Medulla↗